Study Evaluating Safety And Tolerability, Solid Tumor

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT00768469
First received: October 7, 2008
Last updated: May 10, 2012
Last verified: May 2012
  Purpose

This is an open-label, phase 1 study of ascending multiple oral doses of HKI-272 in combination with paclitaxel.


Condition Intervention Phase
Advanced Malignant Solid Tumors
Drug: HKI-272 + Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study Of Neratinib (HKI-272) In Combination With Paclitaxel In Subjects With Solid Tumors

Resource links provided by NLM:


Further study details as provided by Puma Biotechnology, Inc.:

Primary Outcome Measures:
  • The primary objectives are to assess the safety and tolerability, and to decide the recommended dose of HKI-272 in combination with paclitaxel in subjects with advanced solid tumors. [ Time Frame: 19 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary objectives are to obtain the preliminary anti-tumor activity and pharmacokinetic information in subjects with advanced solid tumors. [ Time Frame: 19 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: October 2008
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HKI-272 + Paclitaxel
HKI-272 + Paclitaxel
Drug: HKI-272 + Paclitaxel
HKI-272: 240 mg, continuous daily OD Paclitaxel: 80 mg/m2 IV, day 1, 8, 15 of 28 day cycle
Other Name: Neratinib

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have confirmed pathologic diagnosis of a solid tumor that is not curable with available therapy for which HKI-272 plus paclitaxel is a reasonable treatment option.
  • At least 1 measurable lesion as defined by RECIST criteria.
  • Eastern Cooperative Oncology Group (ECOG) 0 to 1
  • LVEF within institutional limits of normal (by MUGA or ECHO).
  • Screening laboratory values within the following parameters:

    • ANC: greater than or equal to 1.5 x 10E9 /L (1,500 /mm3)
    • Platelet count: 10 x 10E10 /L (100,000 /mm3)
    • Hemoglobin: greater than or equal to 9.0 g/dL
    • Serum creatinine: less than or equal to 1.5 x upper limit of normal (ULN)
    • Total bilirubin: less than or equal to 1.5 xULN · AST and ALT: less than or equal to 2.5 xULN (less than or equal to 5 x ULN if liver metastases are present)
  • For women of child bearing potential, a negative urine or serum pregnancy test result before study entry. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or other means of birth control or whose sexual partners are either sterile or using contraceptives.
  • All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 28 days after the last dose of test article.

Exclusion Criteria:

  • Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m2, epirubicin dose of greater than 800 mg/m2, or the equivalent dose for other anthracyclines or derivatives.
  • Major surgery, chemotherapy, radical (curative intent) radiotherapy, investigational agents, or other cancer therapy within 2 weeks of treatment day 1 or non-recovery from all clinically significant acute adverse effects of prior therapies (excluding alopecia).
  • Subjects with bone or skin as the only site of disease.
  • Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated and have been clinically stable for at least three months, and off steroids or anticonvulsants, before first dose of test article).
  • QTc interval greater than 0.47 second or known history of QTc prolongation or Torsade de Pointes (TdP).
  • Known hypersensitivity to paclitaxel or Cremophor EL (polyoxyethylated castor oil).
  • Pregnant or breast feeding women.
  • Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade greater than or equal to 2 diarrhea of any etiology at baseline).
  • Inability or unwillingness to swallow the HKI-272.
  • Treatment with a taxane within 3 months of treatment day 1.
  • Pre-existing grade 2 or greater motor or sensory neuropathy.
  • Any other cancer within 5 years prior to screening with the exception of contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
  • Presence of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association [NYHA] functional classification of greater than or equal to 2), angina requiring treatment, myocardial infarction within the past 12 months, or any clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.
  • Evidence of significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, make the subject inappropriate for this study. Examples include, but are not limited to, serious active infection (ie, requiring intravenous antibiotic or antiviral agent), uncontrolled major seizure disorder, or significant pulmonary disorder (e.g. interstitial pneumonitis, pulmonary hypertension).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768469

Locations
Japan
Investigational Site
Shizuoka, Japan
Investigational Site
Tokyo, Japan
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
Study Director: Puma Biotechnology
  More Information

No publications provided

Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00768469     History of Changes
Other Study ID Numbers: 3144A2-1115, B1891001
Study First Received: October 7, 2008
Last Updated: May 10, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Puma Biotechnology, Inc.:
HKI-272
Paclitaxel
Combination
Solid Tumor

Additional relevant MeSH terms:
Neoplasms
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014